Quality of Life Scores Remained Different among the Genotypic Groups of Patients with Suspected Hemochromatosis, Even after Treatment Period

Acevedo, Luis Alfredo Utria; Alvarenga, Aline Morgan; Fonseca, Paula Fernanda Silva; Silva, Nathália Kozikas da; Cançado, Rodolfo Delfini; Naoum, Flávio Augusto; Dinardo, Carla Luana; Pereira, Alexandre C.; Brissot, Pierre; Santos, Paulo Caleb Júnior Lima

doi:10.3390/genes13010118

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…A blinded randomised trial of erythrocytapheresis28 in p.C282Y+/+ groups with moderately raised ferritin levels (300 µg/L and 1000 µg/L) did find reduced fatigue scores with transferrin saturations falling from mean 63.5% to 45.4% in the treatment group, although the mean fatigue score was below diagnosis level, making clinical interpretation unclear. Also, recent observational studies have cast doubt on relationships between fatigue, quality-of-life measures and iron parameters in patients with haemochromatosis,29 30 and fatigue might also occur with venesection. A UK Biobank analysis found tiredness genetically linked to factors including increased adiposity, blood lipids and inflammatory markers 31…”

Section: Discussionmentioning

confidence: 99%

HFEgenotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank

Lucas,

Atkins,

Pilling

et al. 2024

BMJ Open

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ObjectivesHFEhaemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.DesignProspective cohort study.Setting22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006–2010).Participants451 270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.Main outcome measuresCox proportional HRs of incident clinical outcomes and mortality in those withHFEp.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years.Results12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% withoutHFEvariants (HR 1.29, 95% CI: 1.12 to 1.48, p=4.7×10-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson’s disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27 to 2.05, p=7.8×10-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.ConclusionsMale and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.

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Section: Discussionmentioning

confidence: 99%

HFEgenotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank

Lucas,

Atkins,

Pilling

et al. 2024

BMJ Open

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“…A blinded randomized trial of erythrocytapheresis (29) in p.C282Y+/+ groups with moderately raised ferritin levels (300 and 1000 µg/L) did find reduced fatigue scores with transferrin saturations falling from mean 63.5% to 45.4% in the treatment group, although the mean fatigue score was below diagnosis level, making clinical interpretation unclear. Also, recent observational studies have cast doubt on relationships between fatigue, quality of life measures and iron parameters in haemochromatosis patients (30) (31) , and fatigue might also occur with venesection. A UK biobank analysis found tiredness genetically linked to factors including increased adiposity, blood lipids and inflammatory markers (32) .…”

Section: Discussionmentioning

confidence: 99%

HFEgenotypes, haemochromatosis diagnosis and clinical outcomes to age 80: a prospective cohort study in UK Biobank

Lucas,

Atkins,

Pilling

et al. 2023

Preprint

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ObjectivesType-1 haemochromatosisHFEgenetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.DesignProspective cohort study.Setting22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010).Participants451,270 participants genetically similar to the 1000-Genomes European reference population, with a mean 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.Main outcome measuresCox proportional hazard ratios of incident clinical outcomes and mortality in those withHFEp.C282Y-p.H63D mutations compared to those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 to 80 years.Results12.1% of p.C282Y+/+ males had baseline (mean age 57) haemochromatosis diagnoses, with age 80 cumulative incidence of 56.4%. 33.1% died vs. 25.4% withoutHFEvariants (Hazard Ratio [HR] 1.29, 95% CI: 1.12-1.48, p=4.7*10-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there was excess delirium, dementia, and Parkinson’s disease, but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of p.C282Y+/+ females had baseline haemochromatosis diagnoses, with cumulative age 80 incidence of 40.5%. There was excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27-2.05, p=7.8*10-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.ConclusionsMale and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.Strengths and limitations of this studyWe analyzed largescale data on community volunteers from the UK Biobank, one of the world’s largestHFEgenotyped cohorts.We have analyzed incident disease outcomes during an extended follow-up period of mean 13.3 years.We have provided the first clinical outcome data to age 80 years in those with haemochromatosis genotypes, including those undiagnosed with haemochromatosis at baseline, expanding the life-course evidence onHFEpenetrance.UK Biobank participants were somewhat healthier than the general population, butHFEallele frequencies were similar to previous UK studies.Incident outcomes were from hospital inpatient and cancer registry follow-up, so did not rely on potentially biased patient self-reporting, but community diagnosed conditions may be underestimated.

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Analysis based on the Pharmacodynamics of Blood Cells using Finite Element Analysis Method(FEM)

et al. 2023

2023 International Conference on Inventive Computation Technologies (ICICT)

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Quality of Life Scores Remained Different among the Genotypic Groups of Patients with Suspected Hemochromatosis, Even after Treatment Period

Cited by 3 publications

References 29 publications

HFEgenotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank

HFEgenotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank

HFEgenotypes, haemochromatosis diagnosis and clinical outcomes to age 80: a prospective cohort study in UK Biobank

Analysis based on the Pharmacodynamics of Blood Cells using Finite Element Analysis Method(FEM)

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